Endogenous neurotensin facilitates enterohepatic bile acid circulation by enhancing intestinal uptake in rats

Initial studies on the digestive hormone neurotensin (NT) showing that inte stinal NT mRNA expression and blood levels were altered in rats fed chow co ntaining bile acid (BA) and the BA chelator cholestyramine led us to invest igate the role of NT in the enterohepatic circulation of BA. In fasted, ane sthetized rats with common bile ducts cannulated for bile collection, intra venous NT infusion (10 pmol.kg(-1).min(-1)) enhanced BA output relative to control over 3 h in animals administered donor bile into the duodenum (30 m ul/min). This suggested that the effect of NT was on the return of BA from the intestine to the liver, which is rate determining in the normal process . In rats prepared as described above and administered [H-3]taurocholate ([ H-3]TC; 5 mM, 1 ml) duodenally, NT infusion (3-10 pmol.kg(-1).min(-1)) incr eased the [H-3]TC recovery rate in bile approximately twofold, whereas sulf ated CCK-8 (12-50 pmol.kg(-1).min(-1)) had no effect. To investigate the ro les of endogenous NT and CCK, we administered [H-3]TC into the rat duodenum or lower jejunum and tested the effect of the NT antagonist SR-48692 (2 nm ol.kg(-1).min(-1)) or CCK-A antagonist lorglumide (100 nmol.kg(-1).min(-1)) . SR-48692 reduced the [H-3]TC recovery rate by congruent to 50% and congru ent to 24% in the duodenum and jejunum, respectively, whereas lorglumide ha d no effect. These results suggest that NT or a similar peptide is an endog enous regulator of enterohepatic BA cycling, which acts by enhancing BA upt ake in the intestine.